A novel X‐linked four‐repeat tauopathy with Parkinsonism and spasticity
Identifieur interne : 000837 ( Main/Exploration ); précédent : 000836; suivant : 000838A novel X‐linked four‐repeat tauopathy with Parkinsonism and spasticity
Auteurs : Parvoneh Poorkaj [États-Unis] ; Wendy H. Raskind [États-Unis] ; James B. Leverenz [États-Unis] ; Mark Matsushita [États-Unis] ; Cyrus P. Zabetian [États-Unis] ; Ali Samii [États-Unis] ; Sophia Kim [États-Unis] ; Nayiry Gazi [États-Unis] ; John G. Nutt [États-Unis] ; John Wolff [États-Unis] ; Dora Yearout [États-Unis] ; J. Lynne Greenup [États-Unis] ; Ellen J. Steinbart [États-Unis] ; Thomas D. Bird [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 2010-07-30.
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Abstract
The parkinsonian syndromes comprise a highly heterogeneous group of disorders. Although 15 loci are linked to predominantly familial Parkinson's disease (PD), additional PD loci are likely to exist. We recently identified a multigenerational family of Danish and German descent in which five males in three generations presented with a unique syndrome characterized by parkinsonian features and variably penetrant spasticity for which X‐linked disease transmission was strongly suggested (XPDS). Autopsy in one individual failed to reveal synucleinopathy; however, there was a significant four‐repeat tauopathy in the striatum. Our objective was to identify the locus responsible for this unique parkinsonian disorder. Members of the XPDS family were genotyped for markers spanning the X chromosome. Two‐point and multipoint linkage analyses were performed and the candidate region refined by analyzing additional markers. A multipoint LODmax score of 2.068 was obtained between markers DXS991 and DXS993. Haplotype examination revealed an ∼20 cM region bounded by markers DXS8042 and DXS1216 that segregated with disease in all affected males and obligate carrier females and was not carried by unaffected at‐risk males. To reduce the possibility of a false‐positive linkage result, multiple loci and genes associated with other parkinsonian or spasticity syndromes were excluded. In conclusion, we have identified a unique X‐linked parkinsonian syndrome with variable spasticity and four‐repeat tau pathology, and defined a novel candidate gene locus spanning ∼28 Mb from Xp11.2–Xq13.3. © 2010 Movement Disorder Society
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DOI: 10.1002/mds.23085
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Leverenz</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>VISN 20 Mental Illness Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Parkinson's Disease Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Matsushita, Mark" sort="Matsushita, Mark" uniqKey="Matsushita M" first="Mark" last="Matsushita">Mark Matsushita</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Parkinson's Disease Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Samii, Ali" sort="Samii, Ali" uniqKey="Samii A" first="Ali" last="Samii">Ali Samii</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Parkinson's Disease Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Kim, Sophia" sort="Kim, Sophia" uniqKey="Kim S" first="Sophia" last="Kim">Sophia Kim</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Gazi, Nayiry" sort="Gazi, Nayiry" uniqKey="Gazi N" first="Nayiry" last="Gazi">Nayiry Gazi</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John G." last="Nutt">John G. Nutt</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Oregon Health Sciences University, Portland, Oregon</wicri:regionArea><placeName><region type="state">Oregon</region></placeName></affiliation></author><author><name sortKey="Wolff, John" sort="Wolff, John" uniqKey="Wolff J" first="John" last="Wolff">John Wolff</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Yearout, Dora" sort="Yearout, Dora" uniqKey="Yearout D" first="Dora" last="Yearout">Dora Yearout</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Greenup, J Lynne" sort="Greenup, J Lynne" uniqKey="Greenup J" first="J. Lynne" last="Greenup">J. Lynne Greenup</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Steinbart, Ellen J" sort="Steinbart, Ellen J" uniqKey="Steinbart E" first="Ellen J." last="Steinbart">Ellen J. Steinbart</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation></author><author><name sortKey="Bird, Thomas D" sort="Bird, Thomas D" uniqKey="Bird T" first="Thomas D." last="Bird">Thomas D. Bird</name><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation><affiliation wicri:level="4"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Washington, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region><settlement type="city">Seattle</settlement></placeName><orgName type="university">Université de Washington</orgName></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington</wicri:regionArea><placeName><region type="state">Washington (État)</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Movement Disorders</title><title level="j" type="abbrev">Mov. Disord.</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-07-30">2010-07-30</date><biblScope unit="volume">25</biblScope><biblScope unit="issue">10</biblScope><biblScope unit="page" from="1409">1409</biblScope><biblScope unit="page" to="1417">1417</biblScope></imprint><idno type="ISSN">0885-3185</idno></series><idno type="istex">C23010745DD4A7B34E18552FA0555AD815AB3908</idno><idno type="DOI">10.1002/mds.23085</idno><idno type="ArticleID">MDS23085</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson's disease/Parkinsonism</term><term>X‐linked Parkinsonism</term><term>X‐linked spastic paraparesis</term><term>genetic linkage</term><term>tauopathy</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The parkinsonian syndromes comprise a highly heterogeneous group of disorders. Although 15 loci are linked to predominantly familial Parkinson's disease (PD), additional PD loci are likely to exist. We recently identified a multigenerational family of Danish and German descent in which five males in three generations presented with a unique syndrome characterized by parkinsonian features and variably penetrant spasticity for which X‐linked disease transmission was strongly suggested (XPDS). Autopsy in one individual failed to reveal synucleinopathy; however, there was a significant four‐repeat tauopathy in the striatum. Our objective was to identify the locus responsible for this unique parkinsonian disorder. Members of the XPDS family were genotyped for markers spanning the X chromosome. Two‐point and multipoint linkage analyses were performed and the candidate region refined by analyzing additional markers. A multipoint LODmax score of 2.068 was obtained between markers DXS991 and DXS993. Haplotype examination revealed an ∼20 cM region bounded by markers DXS8042 and DXS1216 that segregated with disease in all affected males and obligate carrier females and was not carried by unaffected at‐risk males. To reduce the possibility of a false‐positive linkage result, multiple loci and genes associated with other parkinsonian or spasticity syndromes were excluded. In conclusion, we have identified a unique X‐linked parkinsonian syndrome with variable spasticity and four‐repeat tau pathology, and defined a novel candidate gene locus spanning ∼28 Mb from Xp11.2–Xq13.3. © 2010 Movement Disorder Society</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Oregon</li><li>Washington (État)</li></region><settlement><li>Seattle</li></settlement><orgName><li>Université de Washington</li></orgName></list><tree><country name="États-Unis"><region name="Washington (État)"><name sortKey="Poorkaj, Parvoneh" sort="Poorkaj, Parvoneh" uniqKey="Poorkaj P" first="Parvoneh" last="Poorkaj">Parvoneh Poorkaj</name></region><name sortKey="Bird, Thomas D" sort="Bird, Thomas D" uniqKey="Bird T" first="Thomas D." last="Bird">Thomas D. Bird</name><name sortKey="Bird, Thomas D" sort="Bird, Thomas D" uniqKey="Bird T" first="Thomas D." last="Bird">Thomas D. Bird</name><name sortKey="Bird, Thomas D" sort="Bird, Thomas D" uniqKey="Bird T" first="Thomas D." last="Bird">Thomas D. Bird</name><name sortKey="Gazi, Nayiry" sort="Gazi, Nayiry" uniqKey="Gazi N" first="Nayiry" last="Gazi">Nayiry Gazi</name><name sortKey="Greenup, J Lynne" sort="Greenup, J Lynne" uniqKey="Greenup J" first="J. Lynne" last="Greenup">J. Lynne Greenup</name><name sortKey="Kim, Sophia" sort="Kim, Sophia" uniqKey="Kim S" first="Sophia" last="Kim">Sophia Kim</name><name sortKey="Leverenz, James B" sort="Leverenz, James B" uniqKey="Leverenz J" first="James B." last="Leverenz">James B. Leverenz</name><name sortKey="Leverenz, James B" sort="Leverenz, James B" uniqKey="Leverenz J" first="James B." last="Leverenz">James B. Leverenz</name><name sortKey="Leverenz, James B" sort="Leverenz, James B" uniqKey="Leverenz J" first="James B." last="Leverenz">James B. Leverenz</name><name sortKey="Leverenz, James B" sort="Leverenz, James B" uniqKey="Leverenz J" first="James B." last="Leverenz">James B. Leverenz</name><name sortKey="Matsushita, Mark" sort="Matsushita, Mark" uniqKey="Matsushita M" first="Mark" last="Matsushita">Mark Matsushita</name><name sortKey="Nutt, John G" sort="Nutt, John G" uniqKey="Nutt J" first="John G." last="Nutt">John G. Nutt</name><name sortKey="Poorkaj, Parvoneh" sort="Poorkaj, Parvoneh" uniqKey="Poorkaj P" first="Parvoneh" last="Poorkaj">Parvoneh Poorkaj</name><name sortKey="Raskind, Wendy H" sort="Raskind, Wendy H" uniqKey="Raskind W" first="Wendy H." last="Raskind">Wendy H. Raskind</name><name sortKey="Raskind, Wendy H" sort="Raskind, Wendy H" uniqKey="Raskind W" first="Wendy H." last="Raskind">Wendy H. Raskind</name><name sortKey="Raskind, Wendy H" sort="Raskind, Wendy H" uniqKey="Raskind W" first="Wendy H." last="Raskind">Wendy H. Raskind</name><name sortKey="Samii, Ali" sort="Samii, Ali" uniqKey="Samii A" first="Ali" last="Samii">Ali Samii</name><name sortKey="Samii, Ali" sort="Samii, Ali" uniqKey="Samii A" first="Ali" last="Samii">Ali Samii</name><name sortKey="Steinbart, Ellen J" sort="Steinbart, Ellen J" uniqKey="Steinbart E" first="Ellen J." last="Steinbart">Ellen J. Steinbart</name><name sortKey="Wolff, John" sort="Wolff, John" uniqKey="Wolff J" first="John" last="Wolff">John Wolff</name><name sortKey="Yearout, Dora" sort="Yearout, Dora" uniqKey="Yearout D" first="Dora" last="Yearout">Dora Yearout</name><name sortKey="Yearout, Dora" sort="Yearout, Dora" uniqKey="Yearout D" first="Dora" last="Yearout">Dora Yearout</name><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name><name sortKey="Zabetian, Cyrus P" sort="Zabetian, Cyrus P" uniqKey="Zabetian C" first="Cyrus P." last="Zabetian">Cyrus P. Zabetian</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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